Bartonella quintanaLipopolysaccharide Is a Natural Antagonist of Toll-Like Receptor 4

Abstract

Bartonella quintanais a gram-negative microorganism that causes trench fever and chronic bacteremia.B. quintanalipopolysaccharide (LPS) was unable to induce the production of proinflammatory cytokines in human monocytes. Interestingly,B. quintanaLPS is a potent antagonist of Toll-like receptor 4 (TLR4), as it inhibited both mRNA transcription and the release of tumor necrosis factor alpha, interleukin 1β (IL-1β), and IL-6 byEscherichia coliLPS in human monocytes, at ratios ranging from 1,000:1 to 10:1 (B. quintanaLPS toE. coliLPS). Likewise,B. quintanaLPS blocked the interaction ofE. coliLPS with TLR4 in transfected cell lines. The extent of the inhibitory effect ofB. quintanaLPS was demonstrated in microarray studies, which showed downregulation of practically all genes induced by LPS in monocytes. Because of the role of TLR4 in inflammation,B. quintanaLPS may prove useful as a potent anti-TLR4 agent with therapeutic potential in both infections and autoimmune inflammation.